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![Chemical structure of glutaraldehyde (1) and dimethyl suberimidate (2) utilized for amine–amine crosslinking by Torchilin et al. [124, 125]](profile/Seyed-Moghimi/publication/47676993/figure/fig2/AS:339610887573505@1457980953121/Chemical-structure-of-glutaraldehyde-1-and-dimethyl-suberimidate-2-utilized-for.png)
Chemical structure of glutaraldehyde (1) and dimethyl suberimidate (2) utilized for amine–amine crosslinking by Torchilin et al. [124, 125]
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Our ability to engineer nanomaterials for biological and medical applications is continuously increasing, and nanomaterial designs are becoming more and more complex. One very good example of this is the drug delivery field where nanoparticle systems can be used to deliver drugs specifically to diseased tissue. In the early days, the design of the...
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... of the earliest developed methods to covalently couple ligands to the liposome surface is based on amine functionalized liposomes. Torchilin et al. [124,125] Engineering Liposomes and Nanoparticles for Biological Targetingdescribed the use of two homobifunctional crosslinkers (Fig. 1a), glutaraldehyde (1) and dimethyl suberimidate (2) (Fig. 2), for amine-amine crosslinking. Addi- tion of either 1 or 2 to DPPE-containing liposomes resulted in up to 70% imine or amidine formation, respectively, at the liposome surface. Incubation of these liposomes with rabbit anticanine cardiac myosin antibodies at 4°C in aqueous buffer resulted in 60% conversion [125] without loss of the ...
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... Currently, liposomes are far much better than other drug delivery systems, this is because of liposomes are highly biocompatible, and easily biodegraded with minimized cellular toxicity. Since liposomes are self-assembling closed colloidal structures composed of phospholipid bilayers, their surface area can easily be functionalized by PEGylation (PEG) with different functional groups (e.g., amines, alcohols, carboxylic, aldehydes, esters, and thiol-derivatized ligands), and targeting ligands such as peptides, antibodies, or aptamers [87][88][89]. In addition, recent and modern liposomal drug encapsulation strategies allow the effective packaging of both hydrophilic and hydrophobic drugs for theranostic and therapeutic purposes, thus owing to the reduction of long-term systemic toxicity associated with conventional chemotherapeutic drugs such as doxorubicin [64,90]. ...
Globally, cancer is one of the leading causes of death among men and women, it is characterized by the unregulated proliferation of tumor cells. Some of the common risk factors associated with cancer development include the consistent exposure of body cells to carcinogenic agents such as alcohol, tobacco, toxins, gamma rays and alpha particles. Besides the above-mentioned risk factors, conventional therapies such as radiotherapy, and chemotherapy have also been linked to the development of cancer. Over the past decade, tremendous efforts have been invested in the synthesis of eco-friendly green metallic nanoparticles (NPs), and their medical application. Comparatively, metallic NPs have greater advantages over conventional therapies. Additionally, metallic NPs can be functionalized with different targeting moieties e.g., liposomes, antibodies, folic acid, transferrin, and carbohydrates. Herein, we review and discuss the synthesis, and therapeutic potential of green synthesized metallic NPs for enhanced cancer photodynamic therapy (PDT). Finally, the advantages of green hybridized activatable NPs over conventional photosensitizers (PSs) and the future perspectives of nanotechnology in cancer research are discussed in the review. Furthermore, we anticipate that the insights offered in this review will inspire the design and development of green nano-formulations for enhanced image-guided PDT in cancer treatment.
... For functionalizing liposomes, covalent bonding is used to bind ligands to carboxylic acid-modified liposomes, as shown in Fig. (3B) [104]. However, the carboxylic group of the ILs is functionally added to PE-lipids by treating them with various anhydrides in the presence of triethylamine [105]. ...
Cancer has become one of the world's most lethal and life-threatening disorders, resulting in many deaths. Drug targeting and managing drug delivery are concepts that are implemented to increase a drug's therapeutic index by enhancing its specificity to particular cells, tissues, or organs, and reducing its action and harmful side effects. Liposomes have proven to be one of the most innovative drug delivery systems in medicine. Immunoliposomes, also known as antibody-coupled liposomes, have gained a lot of attention as a homing device for targeted therapies. Monoclonal antibodies or antibody fragments that combine with liposomes to create immunoliposomes have been considered a leading technique for targeted delivery. Various functionalization strategies are adopted for the non-covalent and covalent binding of monoclonal antibodies and their components to liposomal surfaces, such as thiolation, amide bonds, hydrazone bonds, and electrostatic interactions, hydrophobic interactions, hydrogen bonding, etc. for cancer-specific targeting. This review emphasized an overview of various stimulus-responsive immunoliposomes capable of regulating drug release in response to an exogenous magnetic field, changes in response stimulation.temperature or pH, enzyme concentration, endogenous stimuli, and applications of immunoliposomes in vaccination and cancer therapeutics and endogenous immune
... It gives an efficient drug carrier system due to their surface similarity with the membrane of living cells, and they show controlled drug release, thereby enhancing the drug availability time (Van Swaay and Demello 2013). These are nonimmunogenic, structurally versatile, nontoxic, fully biodegradable, and most preferably nanocarriers for clinical use (JØlck et al. 2011). Their surface modification is easy; hence, they can be used to modify according to their target (Xie et al. 2005). ...
Neurodegenerative diseases (NDs) such as Alzheimer’s disease, Parkinson’s disease, Huntington disease, amyotrophic lateral sclerosis, and prion disease affect any part of the brain. The complete mechanism of ND is unknown, but there are some molecular mechanism and chemical process. Natural compounds have better compatibility with the human body along with lesser side effects. Moreover, several studies showed that various natural compounds have significant neuroprotective, potent antioxidant, and anti-inflammatory properties, which are effective for treating the different type of ND. In ND, natural compounds act by various mechanisms such as preventing the generation of reactive oxygen species (ROS), eliminating destructed biomolecules before their accumulation affects cell metabolism, and improving the disease conditions. But due to the presence of the blood–brain barrier (BBB) layer and unfavorable pharmacokinetic properties of natural compounds, their delivery into the brain is limited. To minimize this problem and enhance drug delivery into the brain with an effective therapeutic dose, there is a need to develop a practical novel approach. The various studies showed that nanoformulations and microneedles (MN) containing natural compounds such as quercetin, curcumin, resveratrol, chrysin, piperine, ferulic acid, huperzine A, berberine, baicalein, hesperetin, and retinoic acid effectively improved many ND. In this review, the effect of such natural drug-loaded nanoformulation and MN patches on ND management is discussed, along with their merits and demerits. This review aims to introduce different novel approaches for enhancing natural drug delivery into the brain to manage various neurodegenerative diseases.
... Encapsulating a certain drug, usually of a toxic or fragile nature, inside a closed membrane allows for its safe transport across the organism until it reaches its target destination [59,60]. The transport and delivery of the drug is more effective, better controlled and safer through lipid-composition alternations and surface manipulations [61][62][63]. For example, thermosensitive liposomes, formed by mixture of low-temperature sensitive phospholipids, enable the localized release of toxins in the diseased area through temperature manipulation [64]. ...
The cell membrane is a protective barrier whose configuration determines the exchange both between intracellular and extracellular regions and within the cell itself. Consequently, characterizing membrane properties and interactions is essential for advancements in topics such as limiting nanoparticle cytotoxicity. Characterization is often accomplished by recreating model membranes that approximate the structure of cellular membranes in a controlled environment, formed using self-assembly principles. The selected method for membrane creation influences the properties of the membrane assembly, including their response to electric fields used for characterizing transmembrane exchanges. When these self-assembled model membranes are combined with electrophysiology, it is possible to exploit their non-physiological mechanics to enable additional measurements of membrane interactions and phenomena. This review describes several common model membranes including liposomes, pore-spanning membranes, solid supported membranes, and emulsion-based membranes, emphasizing their varying structure due to the selected mode of production. Next, electrophysiology techniques that exploit these structures are discussed, including conductance measurements, electrowetting and electrocompression analysis, and electroimpedance spectroscopy. The focus of this review is linking each membrane assembly technique to the properties of the resulting membrane, discussing how these properties enable alternative electrophysiological approaches to measuring membrane characteristics and interactions.
... In previous studies, NP surface functionalization was performed using chemical reactions such as Michael addition, Cu(I)-catalyzed azide-alkyne cycloaddition, and Cu-free strainpromoted click reaction. [8][9][10][11][12][13][14] To complement to these reactions, in this study, we used a recently reported potassium acyltriuoroborate (KAT) ligation. 15,16 This amide-forming reaction between a KAT derivative and a hydroxylamine (HA) derivative was thought to be suitable for NP functionalization because of the following reasons: (1) the reaction can be performed under biorelevant conditions (in buffer, at near neutral pH, and at room temperature) with fast kinetics even under highly diluted conditions. ...
Low-density lipoprotein (LDL)-mimetic lipid nanoparticles (LNPs), decorated with MRI contrast agents and fluorescent dyes, were prepared by the covalent attachment of apolipoprotein-mimetic peptide (P), Gd(III)-chelate (Gd), and sulforhodamine B (R) moieties on the LNP surface. The functionalized LNPs were prepared using the amide-forming potassium acyltrifluoroborate (KAT) ligation reaction. The KAT groups on the surface of LNPs were allowed to react with the corresponding hydroxylamine (HA) derivatives of P and Gd to provide bi-functionalized LNPs (PGd-LNP). The reaction proceeded with excellent yields, as observed by ICP-MS (for B and Gd amounts) and MALDI-TOF-MS data, and did not alter the morphology of the LNPs (mean diameter: ca. 50 nm), as shown by DLS and cryoTEM analyses. With the help of the efficient KAT ligation, a high payload of Gd(III)-chelate on the PGd-LNP surface (ca. 2800 Gd atoms per LNP) was successfully achieved and provided a high r1 relaxivity (r1 = 22.0 s⁻¹ mM⁻¹ at 1.4 T/60 MHz and 25 °C; r1 = 8.2 s⁻¹ mM⁻¹ at 9.4 T/400 MHz and 37 °C). This bi-functionalized PGd-LNP was administered to three atherosclerotic apoE−/− mice to reveal the clear enhancement of atherosclerotic plaques in the brachiocephalic artery (BA) by MRI, in good agreement with the high accumulation of Gd in the aortic arch as shown by ICP-MS. The parallel in vivo MRI and ex vivo studies of whole mouse cryo-imaging were performed using triply functionalized LNPs with P, Gd, and R (PGdR-LNP). The clear presence of atherosclerotic plaques in BA was observed by ex vivo bright field cryo-imaging, and they were also observed by high emission fluorescent imaging. These directly corresponded to the enhanced tissue in the in vivo MRI of the identical mouse.
... Inserting the azide functional groups after extrusion (post-insertion) rather than co-extruding (pre-insertion) azide-functionalized phospholipids could also help to increase the amount of available azide groups. [76] A study investigating the amount of PEG chain exposed on the surface of liposomes using SANS revealed that post-insertion gave a 14% increase in PEG chain exposure [77]. Another study also revealed that only half of the amount of lipid or polymer was needed to achieve the same nanoparticle zeta potential, indicating that a higher percentage of functional groups were exposed on the surface [78]. ...
Liposomal formulations have important therapeutic applications in anti-cancer treatments but current formulations suffer from serious side effects, high dosage requirements and prolonged treatment. In this study, PEGylated azide-functionalized liposomes containing drug nanocrystals were investigated with the aim of increasing the drug payload and achieving functionalization for targeted delivery. Liposomes were characterized using cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small and ultra-small angle neutron scattering (SANS/USANS) and small and wide angle X-ray scattering (SAXS/WAXS). Cryo-TEM experiments revealed the dimensions of the nanocrystal-loaded liposomes and the change of shape from spherical to elongated after the formation of nanocrystals. Results from SANS/USANS experiments confirmed the asymmetric particle shape. SAXS/WAXS experiments confirmed that the crystalline drug only occurred in freeze-thawed samples and correlated with a new unidentified polymorphic form of ciprofloxacin. Using a small molecule dye, dibenzocyclooctyne (DBCO)-cy5, specific conjugation between DBCO groups and surface azide groups on the liposomes was confirmed; this indicates the promise of this system for tumour-targeted delivery.
... These problems include the following: 1) difficulties associated with the formation of a sufficient functional antibody surface density without inducing excessive bystander activation of the immune responses (an important safety issue), 2) orientation of the antibody and reduction of the functional activity of the antibody that occurs due to chemical conjugation procedures. These problems are difficult to solve even for conventional antibody domains that lack of the Fc region, such as Fabs, diabodies, scFvs, or bispecific antibodies, especially if the antigen-binding molecule exhibits therapeutic activity [61][62][63]. ...
Monoclonal antibodies (mAbs) are an important class of therapeutic agents approved for the therapy of many types of malignancies. However, in certain cases applications of conventional mAbs have several limitations in anticancer immunotherapy. These limitations include insufficient efficacy and adverse effects. The antigen-binding fragments of antibodies have a considerable potential to overcome the disadvantages of conventional mAbs, such as poor penetration into solid tumors and Fc-mediated bystander activation of the immune system. Fragments of antibodies retain antigen specificity and part of functional properties of conventional mAbs and at the same time have much better penetration into the tumors and a greatly reduced level of adverse effects. Recent advantages in antibody engineering allowed to produce different types of antibody fragments with improved structure and properties for efficient elimination of tumor cells. These molecules opened up new perspectives for anticancer therapy. Here we will overview the structural features of the various types of antibody fragments and their applications for anticancer therapy as separate molecules and as part of complex conjugates or structures. Mechanisms of antitumor action of antibody fragments as well as their advantages and disadvantages for clinical application will be discussed in this review.
... In nanomedicine much effort is put into developing better drug delivery systems that can overcome the challenges related to targeting specific tissues and cells for maximum efficacy with the lowest potential for adverse effects as well as protecting the drug from elimination by the immune system (Etheridge et al., 2013;Fichter et al., 2013;Jolck et al., 2011;Malam et al., 2009;Zhao and Rodriguez, 2013). The most promising candidates for such delivery systems include different formulations of liposomes and micelles (Jolck et al., 2011;Malam et al., 2009;Zhao and Rodriguez, 2013). ...
... In nanomedicine much effort is put into developing better drug delivery systems that can overcome the challenges related to targeting specific tissues and cells for maximum efficacy with the lowest potential for adverse effects as well as protecting the drug from elimination by the immune system (Etheridge et al., 2013;Fichter et al., 2013;Jolck et al., 2011;Malam et al., 2009;Zhao and Rodriguez, 2013). The most promising candidates for such delivery systems include different formulations of liposomes and micelles (Jolck et al., 2011;Malam et al., 2009;Zhao and Rodriguez, 2013). In liposomes, lamellar phospholipid bilayers surround aqueous compartments that can be used for cargo and targeting, whereas micelles formed by amphiphilic copolymers can have hydrophilic shells and hydrophobic cores for carrying poorly water soluble drugs. ...
The aim of this study was to compare the effects of cationic micelle and liposome drug delivery systems on liver and lung cells in a toxicological in vitro screening model, with observations on cytotoxicity and genotoxicity. A screening battery was established for assessment of a broad range of parameters related to adverse effects. Clear concentration response effects were observed related to impairment of mitochondrial function, membrane integrity and oxidative stress markers, but no effect was observed on genotoxicity. The adverse effects were highest for the liposomes. The High Content Screening seems optimal for initial screening of adverse effects, and combined with standard cytotoxicity measurements initial screening can be performed for predictive toxicological screening.
... Mouse IgG and STAB-MAb were thiolated with Traut's reagent (10:1 M ratio of Traut's reagent to antibodies in degassed borate buffer, pH 8.3) [33]. After 1 h of incubation at room temperature, unreacted Traut's reagent was removed by Amicon Ultra 15 mL centrifugal filter device (molecular weight cut-off, MWCO, 30 kDa) and the buffer was exchanged with degassed phosphate buffer (pH 7.4). ...
... To that end, we recently reported a functional nanoparticle that responds to the lower pH present in tumors to release its cargo through an increase in particle size from 100 to 1000 nm (expansile nanoparticles [eNPs]), and observed that eNPs localize to peritoneal mesothelioma [15,16] and ovarian carcinomatosis [17] warranting its evaluation in another peritoneal malignancy, PPC. eNPs belong to a family of responsive nanomaterials used for drug delivery [18][19][20][21][22][23][24]. ...
Aim:
To evaluate the tumor localization and efficacy pH-responsive expansile nanoparticles (eNPs) as a drug delivery system for pancreatic peritoneal carcinomatosis (PPC) modeled in nude rats.
Methods & materials:
A Panc-1-cancer stem cell xeno1graft model of PPC was validated in vitro and in vivo. Tumor localization was tracked via in situ imaging of fluorescent eNPs. Survival of animals treated with paclitaxel-loaded eNPs (PTX-eNPs) was evaluated in vivo.
Results:
The Panc-1-cancer stem cell xenograft model recapitulates significant features of PPC. Rhodamine-labeled eNPs demonstrate tumor-specific, dose- and time-dependent localization to macro- and microscopic tumors following intraperitoneal injection. PTX-eNPs are as effective as free PTX in treating established PPC; but, PTX-eNPs result in fewer side effects.
Conclusion:
eNPs are a promising tool for the detection and treatment of PPC.
